title: PrP(Sc)-specific antibodies do not induce prion disease or misfolding of PrP(C) in highly susceptible Tga20 mice.
abstract: Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders caused by misfolding of a cellular protein PrP(C) into an infectious conformation PrP(Sc). Previously our group demonstrated induction of PrP(Sc)-specific antibodies with a SN6b vaccine that targets regions of the protein that are exposed upon misfolding. There are concerns that these antibodies could function as templates to promote misfolding and cause disease. To evaluate the consequences of prolonged exposure to PrP(Sc)-specific antibodies in a prion sensitized animal, tga20 mice were vaccinated with the SN6b vaccine. No clinical signs of disease were detected up to 255 d post-vaccination, and postmortem assay of brains and spleens revealed no proteinase-K resistant PrP. These results suggest that vaccinating against TSEs with the SN6b antigen is safe from the standpoint of prion disease induction.
authors.affiliation: VIDO-InterVac; University of Saskatchewan; Saskatoon, SK CA.
authors.forename: Pekka
authors.initials: P
authors.lastname: Määttänen
authors.affiliation: VIDO-InterVac; University of Saskatchewan; Saskatoon, SK CA; School of Public Health; University of Saskatchewan; SK CA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Taschuk
authors.affiliation: Brain Research Center; University of British Columbia; Vancouver, BC CA.
authors.forename: Li
authors.initials: L
authors.lastname: Ross
authors.affiliation: VIDO-InterVac; University of Saskatchewan; Saskatoon, SK CA; Department of Biochemistry; University of Saskatchewan; Saskatoon, SK CA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Marciniuk
authors.affiliation: Brain Research Center; University of British Columbia; Vancouver, BC CA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bertram
authors.affiliation: VIDO-InterVac; University of Saskatchewan; Saskatoon, SK CA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Potter
authors.affiliation: Brain Research Center; University of British Columbia; Vancouver, BC CA.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Cashman
authors.affiliation: VIDO-InterVac; University of Saskatchewan; Saskatoon, SK CA; School of Public Health; University of Saskatchewan; SK CA; Department of Biochemistry; University of Saskatchewan; Saskatoon, SK CA.
authors.forename: Scott
authors.initials: S
authors.lastname: Napper
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D019286:Endopeptidase K / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D018621:PrPC Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000276:immunology* / Q000378:metabolism; D017096:Prion Diseases / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D017510:Protein Folding; D012608:Scrapie / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000906:Antibodies; D018621:PrPC Proteins; D018620:PrPSc Proteins; D014612:Vaccines; D019286:Endopeptidase K
keywords: disease specific epitope; immunotherapy; misfolding; prion; safety; vaccine